5X5O

Crystal structure of ZAK in complex with compound D2829

Summary for 5X5O

• Entry DOI: 10.2210/pdb5x5o/pdb
• Descriptor: Mitogen-activated protein kinase kinase kinase MLT, N-[2,4-bis(fluoranyl)-3-[2-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]phenyl]-3-bromanyl-benzenesulfonamide (3 entities in total)
• Functional Keywords: zak, kinase, inhibitor, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q9NYL2
• Total number of polymer chains: 1
• Total formula weight: 35856.82

Authors

Dai, Y.B.,Zhao, P.,Yun, C.H. (deposition date: 2017-02-17, release date: 2017-12-27, Last modification date: 2024-03-27)

Primary citation

Chang, Y.,Lu, X.,Shibu, M.A.,Dai, Y.B.,Luo, J.,Zhang, Y.,Li, Y.,Zhao, P.,Zhang, Z.,Xu, Y.,Tu, Z.C.,Zhang, Q.W.,Yun, C.H.,Huang, C.Y.,Ding, K.
Structure Based Design of N-(3-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors.
J. Med. Chem., 60:5927-5932, 2017

PubMed Abstract: A series of N-(3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides were designed as the first class of highly selective ZAK inhibitors. The representative compound 3h strongly inhibits the kinase activity of ZAK with an IC of 3.3 nM and dose-dependently suppresses the activation of ZAK downstream signals in vitro and in vivo, while it is significantly less potent for the majority of 403 nonmutated kinases evaluated. Compound 3h also exhibits orally therapeutic effects on cardiac hypertrophy in a spontaneous hypertensive rat model.

PubMed: 28586211
DOI: 10.1021/acs.jmedchem.7b00572

Experimental method

X-RAY DIFFRACTION (1.868 Å)